The synthesis, processing and translocation of lysosomal enzymes and of their receptor are studied in the normal situation and in genetic disorders of lysosomal function. 1) The receptor is synthesized as a polypeptide of 215,000 daltons; it is glycosylated on asparagine residues and phosphorylated on serine residues. 2) Endocytosed enzyme enters a prelysosomal compartment, which can be separated on Percoll gradients. 3) Liver tissue of patients with I-cell disease have a normal level of many lysosomal enzymes in spite of a deficiency of the P-GlcNAc transferase whch synthesizes the mannose 6-phosphate recognition marker. 4) Studies of the biosynthesis of Beta-hexosaminidase in a cell-free system as well as in intact fibroblasts have revealed a novel defect; in one Tay-Sachs patient, an altered insoluble Alpha-chain is inserted into theendoplasmic reticulum and not transported further. 5) A heritable canine mucopolysaccharidosis has been isentified andshown to be a good biochemical and clinical model for human Alpha-L-iduronidase deficiency mucopolysaccharidosis I, Hurler/Scheie variant).